5-36624000-G-C

Position:

• chr5-36624000-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004172.5(SLC1A3):​c.182-5450G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,048 control chromosomes in the GnomAD database, including 32,274 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32274 hom., cov: 32)
• Consequence: SLC1A3 NM_004172.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

Genes affected

SLC1A3 (HGNC:10941): (solute carrier family 1 member 3) This gene encodes a member of a member of a high affinity glutamate transporter family. This gene functions in the termination of excitatory neurotransmission in central nervous system. Mutations are associated with episodic ataxia, Type 6. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A3	NM_004172.5	c.182-5450G>C		intron_variant		ENST00000265113.9	NP_004163.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A3	ENST00000265113.9	c.182-5450G>C		intron_variant		1	NM_004172.5	ENSP00000265113.4

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98575 AN: 151930 Hom.: 32245 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.685

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.649 AC: 98660 AN: 152048 Hom.: 32274 Cov.: 32 AF XY: 0.654 AC XY: 48626 AN XY: 74300

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.657

Gnomad4 OTH AF: 0.684

Alfa AF: 0.638 Hom.: 3699

Bravo AF: 0.647

Asia WGS AF: 0.730 AC: 2534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.9
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10941306; hg19: chr5-36624102;